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L C Krey

Publications and source records attributed to L C Krey.

At least 37 records · Page 2Linked to original sources
PubMed1990

Progesterone modulation of gonadotropin secretion by dispersed rat pituitary cells in culture. III. A23187, cAMP, phorbol ester and DiC8-stimulated luteinizing hormone release.

Dispersed estradiol-treated rat pituitary cells were used to characterize progesterone (P) modulation of luteinizing hormone (LH) secretion in response to a variety of pharmacologic secretagogues which influence cell biochemistry. Acute (less than 3 h) and chronic (24 h) exposures to P prior to secretagogue challenge respectively enhanced and inhibited Ca2+ ionophore (A23187)-stimulated and gonadotropin-releasing hormone (GnRH)-stimulated LH release in similar quantitative fashion without any effect on concurrent prolactin release. Similar responses were also noted with cholera toxin-stimulated secretion. However, when protein kinase C activators such as phorbol esters and dioctanoylglycerol were used to trigger LH release, chronic exposure to P did not inhibit, but rather enhanced, LH release. Again, P had no effect on prolactin release. 'Washout' studies indicated that chronic treatments with P would suppress LH secretion stimulated by these compounds, but only when the steroid was cleared from the cells 4 h beforehand. These studies provide further evidence that P specifically modulates gonadotroph secretory function via mechanisms which bypass GnRH receptors. Moreover, they suggest that P exerts many different actions within the gonadotroph and question the role of protein kinase C in GnRH action.

Animals↗
PubMed1990

Progesterone modulation of gonadotropin secretion by dispersed rat pituitary cells in culture. I. Basal and gonadotropin-releasing hormone-stimulated luteinizing hormone release.

Dispersed, estradiol-treated, rat pituitary cells were cultured to characterize the influences of a physiologic concentration of progesterone (P, 10(-7) M) on gonadotroph responsiveness to gonadotropin-releasing hormone (GnRH). Acute (less than 6 h) P treatment enhanced and chronic (greater than 12 h) treatment suppressed both basal and GnRH-stimulated luteinizing hormone (LH) release. This modulation took place without any change in intracellular LH stores, indicating that the secretory changes are not attributable to changes in LH synthesis, and were not accompanied by similar alterations in basal or thyrotropin-releasing hormone-stimulated prolactin secretion. Moreover, the timing of these responses was fixed since a 10-fold lower P concentration produced only smaller and briefer alterations in LH release. Analyses of the temporal characteristics of effective P stimuli indicated that a brief 6 h exposure to P inhibited GnRH-stimulated LH secretion 18 h later. In contrast, P's acute actions rapidly dissipated following removal of the steroid from the culture medium. Finally, P-induced enhancement and suppression of GnRH-stimulated LH release could be blocked by appropriately timed treatments with protein synthesis inhibitors. Our findings are consistent with the hypothesis that P influences gonadotroph secretory function via the production of specific proteins.

Animals↗
PubMed1990

Progesterone modulation of gonadotropin secretion by dispersed rat pituitary cells in culture. II. Intracellular metabolism and progestin receptors.

Dispersed, estradiol (E2)-treated, rat pituitary cell cultures were used to examine the intracellular processing of progesterone (P) associated with its modulation of gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) secretion. Enhancement and suppression of LH release was only observed with acute and chronic exposures to P or other naturally occurring and synthetic progestins avidly bound by pituitary progestin receptors; such responses were inhibited by cotreatment with the antiprogestin RU486 but not with the antiandrogen flutamide, illustrating the importance of the P + receptor interactions. However, cotreatment with a 100-fold molar excess of the 5 alpha-reductase inhibitor 17 beta-N,N-diethyl-carbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA) had no effect on the expression of P's modulatory actions. Additional studies using different E2 pretreatments revealed that P enhanced LH release when progestin receptor levels were elevated. Moreover, the magnitude and duration of P's influences on LH release increased in cells with higher receptor levels. However, there were several instances in which progestin receptor level and P modulation of LH release did not correlate. In several instances E2-induced progestin receptor levels stabilized at a maximal level whereas P enhancement of LH secretion continued to increase in size and duration. These findings underscore the importance of progestin receptors for P-induced modulation of LH secretion and illustrate that 5 alpha-reduction and further metabolism of P is not obligatory for the expression of these responses. In addition, our data demonstrate that the important cellular mechanisms underlying E2 priming of gonadotroph responsiveness to P entail the induction of progestin receptor levels and other as yet unidentified cellular processes.

Androgen Antagonists↗
PubMed1990

Time-courses of the appearance/disappearance of nuclear androgen + receptor complexes in the brain and adenohypophysis following testosterone administration/withdrawal to castrated male rats: relationships with gonadotropin secretion.

We characterized the temporal dynamics of brain and pituitary cell nuclear androgen receptor binding and serum androgen and gonadotropin levels associated with the implantation and removal of testosterone (T)-filled Silastic capsules into performed s.c. flank pouches of castrated, awake male rats. These capsules produced serum T levels in the physiologic range. The number of cell nuclear androgen + receptor complexes, as measured in an exchange assay using [3H]R1881, increased 15-fold at 0.5 h after capsule insertion in the HPAS (combined hypothalamus, preoptic area, amygdala and septum) and anterior pituitary gland, but then showed a second progressive rise within the next 8 h. This pattern suggests that T exerts an initial action in the tissues to alter the affinity and/or number of available androgen receptors. There was a lag time of 2-4 h to the first indication of negative feedback suppression of LH secretion. Serum LH levels declined only slightly at 4 h after capsule insertion but continued to fall thereafter, reaching undetectable values by 24 h. In contrast, serum FSH levels declined only slightly after 24 h of T exposure. After removal of the T capsules, serum T levels declined to castrate values within 2 h at which time the level of androgen + receptor complexes had fallen to 60% in the brain and pituitary. Serum LH and FSH concentrations were unchanged at 2 h after capsule removal, but rose significantly within the next 2 h. The data indicate that the occupation of androgen receptors rapidly changes in response to variations in circulating T in a fashion that implicates their involvement in the expression of this steroid's negative feedback actions on gonadotropin secretion.

Androgens↗
PubMed1990

Estradiol processing by pituitary cells in culture: an examination of the influences of various exposures to progesterone.

Dispersed, estradiol (E2)-treated pituitary cells were used to examine the cellular mechanisms underlying progesterone (P) suppression of GnRH-stimulated LH and FSH secretion. When cells were exposed to 10(-9) M E2 for 48 h prior to GnRH challenge, P (10(-7) M) treatment for the last 24 h suppressed gonadotroph responsiveness to GnRH for both LH and FSH secretion (gonadotropin released/intracellular stores of gonadotropin available for release). To determine if P acts by blocking E2 processing and/or uptake, we exposed cells to 2,4,6,7-3H-E2 +/- P and monitored the level and distribution of 3H-estrogens bound to estrogen receptors salt-extracted from nuclear pellets purified by sucrose density centrifugation. At 1, 4 and 24 h, P had no effect on the level of 3H-estrogen+receptor complexes or on the distribution of receptor-bound 3H-E2, 3H-estrone and 3H-estriol. The results indicate that chronic influences of P to suppress the responsiveness of E2-treated gonadotrophs to GnRH cannot be explained by alterations in estrogen receptor occupation as is the case in reproductive tract tissues.

Animals↗
PubMed1989

Cobalt-protoporphyrin suppresses testosterone secretion by multiple interactions within the brain-pituitary-testicular axis.

Administration of large doses of cobalt-protoporphyrin (CoPP), a synthetic heme analogue, to adult male rats leads to a rapid decline in serum concentrations of testosterone and luteinizing hormone (LH). Hypothalamic luteinizing hormone-releasing hormone (LHRH) contents are not affected by CoPP. The pituitary LH response to exogenous LHRH is attenuated by CoPP both in vivo and in vitro in pituitary cultures. Additionally, CoPP directly inhibits synthesis or release of testosterone by the testes. These effects are specific to CoPP and not shared by heme, inorganic cobalt or tin-protoporphyrin. Castration of CoPP-treated rats leads to a normal rise in LH concentrations, but this can be abolished by using testosterone implants to elevate serum testosterone concentrations to the low levels (approximately 0.4 ng/ml) typical of CoPP-treated intact rats. Thus, CoPP appears to be a pharmacological model for testing the mechanisms which underlie an enhanced negative feedback efficacy of testosterone on pituitary LH release.

Animals↗
PubMed1989

Effects of daylength on androgen metabolism and pulsatile luteinizing hormone secretion in male golden hamsters.

In an effort to understand the potential neuroendocrine mechanisms underlying photoperiodic control of fertility in seasonally breeding species, we monitored the intracellular processing and nuclear uptake of [1 alpha, 2 alpha-3H]testosterone (3H-T) within the brain-pituitary complex as well as the patterns of episodic luteinizing hormone (LH) secretion in male golden hamsters exposed to long day (14 h light:10 h dark) and short day (10 h light:14 h dark) photoperiods. Target tissue specific patterns of nuclear 3H-androgens and estrogens were observed in castrated, T-replaced hamsters exposed to long and short days for 7 weeks or longer. Significantly, 3H-T metabolism or receptor-mediated nuclear uptake in the hamsters in short days was not influenced in any manner that would explain their increased responsiveness to androgen feedback suppression of LH release. Comparable patterns of episodic LH secretion were observed in acutely catheterized hamsters castrated for 7 weeks prior to exposure to 8 weeks of long or short days. Similar patterns were also observed in animals maintained in long days and castrated 1 or 2 weeks prior to blood collection. However, such a pattern was not seen in acutely castrated hamsters maintained in the short-day photoperiod. The data suggest that steroid-independent mechanisms play an important role in suppressing gonadotropin release in short days in this species. However, such mechanisms appear to be most effective when the animals are or have recently been exposed to circulating androgens.

Androgens↗
PubMed1988

Influences of photoperiod on nuclear androgen receptor occupancy in neuroendocrine tissues of the golden hamster.

Day length regulates the negative feedback potency of gonadal steroids upon luteinizing hormone (LH) in seasonal breeders such as the golden hamster. We have used an exchange assay employing 3H-R1881 to determine whether nuclear androgen plus receptor levels in the preoptic area, medial basal hypothalamus, or anterior pituitary differ between male hamsters maintained in long or short days. Cell nuclear androgen plus receptor levels in brain and anterior pituitary were significantly lower in intact males maintained in short days; these differences reflected significant decreases in testis size and serum testosterone (T levels upon exposure to inhibitory photoperiods. In castrated males in which serum T levels were 'clamped' by the insertion of T-filled Silastic capsules, exposure to short days was not correlated with an increase in preoptic area, medial basal hypothalamus, or anterior pituitary receptor occupancy even though T's negative feedback actions upon LH were clearly enhanced. In contrast, there were instances in which androgen receptor occupation was elevated in males exposed to long days. Our results suggest that in the male golden hamster, the well-documented increase in the ability of T to suppress LH secretion in short photoperiods cannot be attributed to an increase in receptor-mediated uptake and nuclear accumulation of androgen in target cells in the brain and anterior pituitary gland.

Animals↗
PubMed1988

Stress-induced suppression of luteinizing hormone concentrations in wild baboons: role of opiates.

Numerous stressors disrupt male reproductive physiology; previous studies of a population of wild baboons, living freely in a national park in East Africa, indicated that the stress of anesthetization by phencyclidine darting decreased both LH secretion and testicular sensitivity to LH. This study was undertaken to determine the mechanism(s) of the decreased LH secretion in these animals. Neither stress-induced glucocorticoid nor catecholamine release was responsible, since neither blockade of glucocorticoid secretion with the adrenal steroidogenesis inhibitor metyrapone nor blockade of catecholamine secretion with the sympathetic ganglionic blocking drug chlorisondamine prevented the stress-induced decline in serum LH concentrations. Administration of the opiate receptor antagonist naloxone (0.5 mg/kg BW), however, not only prevented the decline, but also transiently elevated serum LH concentrations, suggesting that opiates play a role in tonic as well as stress-induced decreases in LH secretion. Administration of a small dose of naloxone (0.03 mg/kg BW) commensurate with occupancy of only mu-opiate receptors slowed the stress-induced decline in LH concentrations, as did administration of the kappa-receptor antagonist MR 1452. These data suggest that opiates inhibit LH release via the combined occupancy of both mu- and kappa-receptors.

Animals↗
PubMed1987

Effect of progesterone on monoamine turnover in the brain of the estrogen-primed rat.

The effect of progesterone (P) on monoamine levels and turnover was evaluated in 8 brain nuclei in estrogen-primed rats. Animals were subcutaneously (SC) injected with P or vehicle 21 hours after SC treatment with 5 micrograms of estradiol benzoate (EB). EB-primed animals treated with P showed high levels of lordosis behavior and an LH surge three hours later. Initial concentrations of norepinephrine (NE), dopamine (DA), serotonin (5HT) and 5-hydroxyindole acetic acid were determined in EB-saline treated controls 3 hours after P or vehicle. NE and DA turnover was estimated from the exponential decline of these amines 2 hours after IP injection of alpha-methyl-p-tyrosine (5 hours after P or vehicle). The accumulation of 5HT 20 min following IP injection of pargyline was used as an index of 5HT turnover. P did not affect the initial NE, 5HT or 5HIAA concentrations in any of the brain nuclei studied, but decreased DA content in the arcuate-median eminence region (Ar-ME). The DA rate constant was elevated in the nucleus of the diagonal band of Broca and the DA turnover rate was decreased in the Ar-ME. In the periventricular region (PVE, anterior hypothalamic level) the NE turnover rate (K, pg/microgram protein/hr) and rate constant (k, hr-1) decreased following P treatment. Progesterone treatment decreased the accumulation of 5HT in the ventromedial hypothalamus (VMN, pars lateralis) and the dorsal midbrain central grey (MCG). Progesterone effects on monoamine turnover were not found in the lateral septal, medial preoptic, anterior hypothalamic or dorsal raphe nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Biochemical and radioautographic analysis of estrogen-inducible progestin receptors in female ferret brain and pituitary: correlations with effects of progesterone on sexual behavior and gonadotropin-releasing hormone-stimulated secretion of luteinizing hormone.

Cytosolic binding molecules for the synthetic progestin [3H]R5020, were isolated in vitro from several brain regions including preoptic area/anterior hypothalamus, mediobasal hypothalamus, medial amygdala and parietal cortex as well as the pituitary gland of ovohysterectomized female ferrets. Binding of [3H]R5020 to cortical cytosols was saturable, of high affinity (apparent dissociation constant of 2.0 nM), and was steroid specific. Pretreatment of ferrets with a Silastic capsule containing estradiol caused significant increments in the concentration of cytosolic R5020 binding sites in hypothalamus and pituitary gland, but not in the other brain regions studied. Brains of additional ovohysterectomized ferrets, which had been primed with estradiol prior to receiving an i.v. injection of [3H]R5020, were processed radioautographically. Intense labeling of cells was seen in the medial and lateral preoptic area, in the lateral hypothalamus, and in the ventromedial and arcuate nuclei of the hypothalamus. Radioautograms from the brains of additional ovohysterectomized ferrets given an i.v. injection of [3H]estradiol revealed labeled cells in all of the above regions, in addition to the basolateral portion of the septum, the bed nucleus of the stria terminalis, and in the anterior amygdaloid area as well as the medial and cortical nuclei of the amygdala. This distribution of neural progestin and estrogen binding sites resembles those previously reported for these steroids in the rat, guinea pig, hamster and macaque. Functional studies showed that acute s.c. implantation of a Silastic capsule containing progesterone to ovohysterectomized ferrets, which had been primed with a low dosage of estradiol, failed to augment their sexual receptivity in limited tests with stimulus males given 4 and 8 h after progesterone treatment. This result contrasts with the well-established facilitatory effect of progesterone on sexual receptivity in rat and guinea pig. Chronic exposure to a progesterone capsule caused significant reductions in sexual receptivity in ovohysterectomized ferrets which were implanted concurrently with a second Silastic capsule containing a high dosage of estradiol. Similar effects of progesterone have been reported in rat and guinea pig, but not in the rhesus monkey. Thus species differences in the ability of progesterone to facilitate or inhibit sexual receptivity are not readily explained by species differences in the neural distribution of estrogen-induced progestin receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

1,25-Dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei.

To better understand the role of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in brain function, the level of calcium-binding protein (CaBP) and the activities of choline acetyltransferase (CAT) and monoamine oxidase were measured in discrete brain nuclei of vitamin D-deficient and -replete male rats. The nuclei sampled were those in which receptors for 1,25-(OH)2D3 and/or vitamin D-dependent CaBP have been localized. Significant elevations in CAT activity were found in the arcuatemedian eminence and in the bed nucleus of the stria terminalis of rats made vitamin D replete by eight daily ip injections of 100 or 200 ng 1,25-(OH)2D3 as well as by constant intraventricular (ivi) infusion of 25 ng 1,25-(OH)2D3 for 7 days. The percent increase ranged from 12-45% and was related to the ip dose administered. Constant ivi of 2 mM CA2+ or 125 ng 25-hydroxyvitamin D3/day for 7 days did not alter CAT activity. No significant changes in monoamine oxidase or CaBP in discrete brain nuclei were observed with vitamin D repletion. Since the arcuate-median eminence of the hypothalamus is an important regulatory site in the neuroendocrine control of reproduction, serum testosterone was measured. Serum testosterone levels were abnormally low in the vitamin D-deficient animals, but increased 2- to 5-fold to normal values in those rats made vitamin D replete by constant ivi of 25 ng 1,25-(OH)2D3 or by ip injection of 100 or 200 ng 1,25-(OH)2D3. Patterns of serum LH paralleled those for testosterone. Our results suggest that 1,25-(OH)2D3 effects cholinergic activity in several discrete brain regions and may play a role in the neuroendocrine regulation of certain aspects of anterior pituitary gland function.

Animals↗
PubMed1986

Are catechol oestrogens obligatory mediators of oestrogen action in the central nervous system? I. Characterization of pharmacological probes with different receptor binding affinities and catechol oestrogen formation rates.

In an attempt to define pharmacological probes with which to test the role of catechol oestrogen formation in the central nervous system, five oestrogens (oestradiol-17 beta, oestradiol-17 alpha, 4-fluoro-oestradiol, 2-fluoro-oestradiol and moxestrol (11 beta-methoxy-17 alpha-ethynyloestradiol) were studied for binding to oestrogen receptors and conversion to catechol metabolites. Binding to cytosol oestrogen receptors was measured in the hypothalamus-preoptic area-amygdala (HPA), pituitary gland and uterus of ovariectomized rats. Conversion to catechol oestrogens was tested in microsomes from the HPA, pituitary gland and liver, using a catechol-O-methyltransferase-coupled radioenzymatic assay. Oestradiol-17 alpha was the only weak oestrogen receptor ligand. Binding affinities of the other compounds tested were much higher and comparable to those of oestradiol-17 beta. In contrast, oestradiol-17 alpha was rapidly converted to catechol metabolites, while moxestrol was a relatively poor substrate for catechol oestrogen formation. 4-Fluoro-oestradiol could be 2-hydroxylated but not 4-hydroxylated. 2-Fluoro-oestradiol exhibited impaired 2-hydroxylation but normal 4-hydroxylation.

Animals↗
PubMed1986

Are catechol oestrogens obligatory mediators of oestrogen action in the central nervous system? II. Potencies of natural and synthetic oestrogens for induction of gonadotrophin release and female sexual behaviour in the rat.

The role of catechol oestrogen formation in the mechanism by which circulating oestrogens facilitate gonadotrophin release and female sexual behaviour was explored in adult female rats. The effects of oestradiol-17 beta were compared with those of a group of oestrogens with either a reduced affinity for oestrogen receptors (oestradiol-17 alpha) or a reduced ability to act as substrates for catechol oestrogen formation (2-fluoro-oestradiol, 4-fluoro-oestradiol and moxestrol (11 beta-methoxy-17 alpha-ethynyloestradiol]. Rats were ovariectomized on the evening of dioestrus day 1 of the 4-day oestrous cycle and implanted s.c. 12 h later with infusion pumps containing either one of the test oestrogens or vehicle alone. Infusion rates for oestradiol-17 beta, moxestrol, 2-fluoro-oestradiol and 4-fluoro-oestradiol were adjusted to give concentrations of nuclear oestrogen receptors in the brain and pituitary gland within the range of those found in intact female rats during pro-oestrus. Oestradiol-17 alpha was infused at the same and at a tenfold higher rate than that of oestradiol-17 beta; neither of these treatments with oestradiol-17 alpha significantly increased brain or pituitary gland nuclear oestrogen receptor levels. On the day after the pump was implanted, samples of tail vein blood were withdrawn at 12.00, 14.00, 16.00 and 18.00 h for LH assay. All animals were then injected s.c. with 1 mg progesterone in propylene glycol, and tested for feminine sexual behaviour 5 h later. Oestradiol-17 beta, moxestrol, 2-fluoro-oestradiol and 4-fluoro-oestradiol all elicited pronounced LH surges and facilitated progesterone-triggered proceptive and lordosis behaviours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging.

The hippocampus of the rat loses neurons with age, a loss which may eventuate in some of the functional impairments typical of senescence. Cumulative exposure to corticosterone (CORT) over the lifespan may be a cause of this neuronal loss, as it is prevented by adrenalectomy at mid-age. In this study, we demonstrate that prolonged exposure to CORT accelerates the process of cell loss. Rats were injected daily with sufficient CORT to produce prolonged elevations of circulating titers within the high physiological range. Animals treated for 3 months (chronic subjects) resembled aged rats in a number of ways. First, both groups had extensive and persistent depletions of CORT receptors in the hippocampus; in the case of chronic rats, no recovery of receptor concentrations occurred 4 months after the end of steroid treatment. Second, autoradiographic analysis revealed that the receptor depletion was due, in part, to a loss of CORT-concentrating cells, especially in the CA3 cell field. Remaining cells bound significantly less [3H]corticosterone than did those of control rats. Finally, analysis of size distributions of hippocampal cell bodies indicated that chronic subjects lost neurons of the same size as those lost in the aged hippocampus. Furthermore, chronic subjects also had increased numbers of small, darkly staining cells of CA3; these corresponded in size to the dark glia whose numbers increase in the aged hippocampus, and which are thought to infiltrate in response to neuronal damage or destruction. Thus, this study supports the hypothesis that cumulative exposure to CORT over the lifespan may contribute to age-related loss of neurons in the hippocampus, and that prolonged stress or exposure to CORT accelerates this process.

Aging↗
PubMed1984

Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response.

The hippocampus is the principal target site in the brain for adrenocortical steroids, as it has the highest concentration of receptor sites for glucocorticoids. The aged rat has a specific deficit in hippocampal glucocorticoid receptors, owing in large part to a loss of corticoid-sensitive neurons. This deficit may be the cause for the failure of aged rats to terminate corticosterone secretion at the end of stress, because extensive lesion and electrical stimulation studies have shown that the hippocampus exerts an inhibitory influence over adrenocortical activity and participates in glucocorticoid feedback. We have studied whether it is the loss of hippocampal neurons or of hippocampal glucocorticoid receptors in the aged rat that contributes most to this syndrome of corticosterone hypersecretion. To do this, we used two model systems for producing reversible glucocorticoid receptor depletion in the hippocampus, and we found that depletion of receptors without inducing cell loss results in corticosterone hypersecretion. Furthermore, correction of the receptor deficit results in normalization of corticosterone secretion. These results focus attention on the hippocampus as an important glucocorticoid sensor in relation to the stress response. They also provide important new physiological correlates for the remarkable plasticity of the hippocampal glucocorticoid receptor system, which is under independent control by corticosterone and by vasopressin.

Adrenal Cortex↗
PubMed1984

Stress down-regulates corticosterone receptors in a site-specific manner in the brain.

We have examined whether corticosterone receptor number within the brain can be regulated by its own ligand and whether such autoregulation reduces receptor number after the sustained secretion of corticosterone during repeated stress. Glucocorticoid receptors were measured in cytosolic preparations from acutely adrenalectomized rats using [1,2,6,7-3H] dexamethasone; maximal binding and receptor affinity parameters were determined by Scatchard analysis. Sustained elevations of circulating corticosterone, whether by repeated stress or exogenous corticosterone administration, did not change receptor affinity for [3H]dexamethasone, but significantly reduced cytosolic corticosterone receptor number. This reduction in total receptor number could not be attributed to residual tissue contamination with endogenous corticosterone after adrenalectomy or to translocation of cytosolic receptors to cell nuclei. The receptor reductions were anatomically specific, occurring in the hippocampus and amygdala, but not in the hypothalamus or pituitary, and were limited, in that exogenous corticosterone plus stress reduced receptor number no more than did stress alone. Further, 3 weeks of daily administration of 5 mg corticosterone caused reductions similar to those seen after only 4 days of treatment. Finally, the declines in glucocorticoid receptor number were reversible; receptor concentrations returned to normal levels within 1 week after the cessation of treatment with exogenous corticosterone. Thus, this study presents evidence that glucocorticoid down-regulation may constitute a physiological phenomenon.

Animals↗